Results from previous studies in our laboratory and others demonstrate that, similar to systemic arteries, the mechanical responses of pulmonary vessels to several endogenous and exogenous substances can be markedly influenced by the endothelium. Hence, pulmonary endothelium may have a potentially important role in regulation of the pulmonary circulation and may be involved in the circulatory changes which occur during hypoxia, pulmonary hypertension and acute respiratory distress syndrome. However, due to limited information currently available regarding endothelium-vascular smooth muscle interactions which apparently occur in both pulmonary arteries and veins, the above possibilities remain highly speculative. Much additional basic information from both in vivo and in vitro studies is needed to evaluate possible involvement of endothelium-vascular smooth muscle interactions in the changes which occur in the pulmonary circulation under physiological and pathophysiological conditions. The purpose of present study is to continue ongoing investigation of the influences of endothelium on the vasoreactivity of pulmonary arteries and veins and to expand our studies into the mechanisms whereby such interactions occur. Briefly, we propose to continue in vitro studies using bovine vessels to compare pulmonary arteries and veins with regard to: 1) the influence of endothelium on basal mechanical activity and responses to endogenous and exogenous vasodilators and vasoconstrictors at various levels in the arterial and venous beds; 2) differention of the mechanisms involved using various inhibitors and cross-over "sandwich type" experiments between arteries and veins; 3) the potential role of cyclic nucleotides in mediating observed effects; and 4) the potential role of endothelium in modifying or mediating resonses of the vessels during hypoxia. In addition, limited similar studies are proposed for comparative purposes using systemic arteries and veins as well as pulmonary arteries and veins isolated from another mammalian species. Based upon results already obtained in our laboratory, it is anticipated that results from the proposed studies will document marked differences in the endothelial-smooth muscle cell interactions between pulmonary arteries and veins.